Alzheimer's disease is the primary cause of dementia and imposes a significant socioeconomic burden globally.Physical exercise,as an effective strategy for improving general health,has been largely reported for it...Alzheimer's disease is the primary cause of dementia and imposes a significant socioeconomic burden globally.Physical exercise,as an effective strategy for improving general health,has been largely reported for its effectiveness in slowing neurodegeneration and increasing brain functional plasticity,particularly in aging brains.However,the underlying mechanisms of exercise in cognitive aging remain largely unclear.Adiponectin,a cell-secreted protein hormone,has recently been found to regulate synaptic plasticity and mediate the antidepressant effects of physical exercise.Studies on the neuroprotective effects of adiponectin have revealed potential innovative treatments for Alzheimer's disease.Here,we reviewed the functions of adiponectin and its receptor in the brains of human and animal models of cognitive impairment.We summarized the role of adiponectin in Alzheimer's disease,focusing on its impact on energy metabolism,insulin resistance,and inflammation.We also discuss how exercise increases adiponectin secretion and its potential benefits for learning and memory.Finally,we highlight the latest research on chemical compounds that mimic exerciseenhanced secretion of adiponectin and its receptor in Alzheimer's disease.展开更多
Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitatio...Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.展开更多
Background:Activation of NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)inflammasomes induced by pyroptosis is crucial in metabolic dysfunction-associated steatohepatitis(MASH)progression.Adiponectin possesses a...Background:Activation of NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)inflammasomes induced by pyroptosis is crucial in metabolic dysfunction-associated steatohepatitis(MASH)progression.Adiponectin possesses an anti-inflammatory role in various liver diseases.This study aimed to evaluate the effects of adiponectin on MASH.Methods:Adiponectin-mediated anti-inflammatory mechanisms,effects on pyroptosis-related proteins,and activation of NLRP3 inflammasomes were investigated using methionine-choline-deficient(MCD)-induced MASH murine model and in vitro models.The degree of MASH inflammation in liver tissue of C57BL/6J mice was assessed using histopathology.Enzyme-linked immunosorbent assay was performed to measure levels of inflammatory factors[interleukin-18(IL-18),IL-1β,and tumor necrosis factor-α(TNF-α)]in mice serum and culture medium.Western blot and quantitative polymerase chain reaction were performed to analyze the expression of pyroptosis-related genes and proteins in liver tissues of mouse model and in vitro models.Macrophage recruitment in vitro was evaluated using co-culture of upper and lower chambers.Results:MASH developed in MCD diet mice[metabolic dysfunction-associated steatotic liver disease(MASLD)activity score=6]but not in methionine-choline-sufficient(MCS)diet mice(MASLD activity score=3).Compared to MCS-fed mice,MCD-fed mice showed increased serum levels of aspartate amino-transferase,IL-18,IL-1β,and TNF-αand higher MASLD activity score(P<0.001).Adiponectin inhibited these increases(P<0.05)and suppressed mRNA and protein levels of NLRP3,gasdermin-D(GSDMD),and GSDMD-N in liver tissues(P<0.05).In vitro,lipopolysaccharide(LPS)/palmitic acid(PA)increased the levels of IL-18,IL-1β,and TNF-α,mRNA expressions of CASP1 and GSDMD,and production of CASP1,NLRP3,GSDMD,and GSDMD-N(P<0.01).Adiponectin reduced the levels of these inflammatory fac-tors and downregulated the mRNA expression and protein generation of pyroptosis-related markers(P<0.05).HepG2 cells pretreated with LPS/PA recruited more J774A.1 cells(P<0.001)and increased inflam-matory factor secretion by J774A.1 cells(P<0.001).Adiponectin inhibited this recruitment and reduced inflammatory factor secretion(P<0.001).Conclusions:Adiponectin inhibits hepatocyte pyroptosis by reducing the production and activation of NLRP3 inflammasomes,CASP1,and GSDMD,thus improving the inflammatory response in MASH and possibly delaying or reversing MASLD progression.展开更多
BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can pre...BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can predict all-cause mortality and major adverse CV events(MACE)in patients with coronary artery disease(CAD)and to determine the prognostic value of adiponectin in predicting all-cause mortality and MACE in patients with stable CAD.METHODS We conducted a systematic search on PubMed,Scopus,and Google Scholar to find relevant studies published through June 2023 evaluating the long-term prognostic role of adiponectin in patients with stable CAD.Using a random effects model with 95%CI,we estimated the odds ratio(OR)while assessing heterogeneity through I^(2)statistics.To ensure robustness,we performed a sensitivity analysis using the leave-one-out approach.RESULTS After screening,we included five prospective studies involving 3225 patients who were followed up for a median duration of 3.8 years.Within the study population,prevalent risk factors included hypertension,diabetes,hyperlipidemia,and smoking.The commonly prescribed medications were angiotensin-converting enzyme inhibitors,beta blockers,and statins.The combined adjusted OR for all-cause mortality was found to be 2.51(95%CI:1.36–4.62),showing heterogeneity(I^(2)=65.51%,P=0.03).On the other hand,the combined adjusted OR for MACE was determined to be 1.04(95%CI:1.02–1.06)with no significant heterogeneity observed(I^(2)=0%,P=0.68).Through a sensitivity analysis,it was discovered that none of the studies significantly impacted the overall results of the meta-analysis,thus indicating their robustness.CONCLUSION Higher levels of adiponectin were found to be associated with an increased risk of long-term mortality and MACE in patients with CAD,which highlights its potential as a cost-effective marker for risk assessment and guiding treatment strategies.Further research on the role of adiponectin could greatly influence decision-making and resource allocation in CV care.展开更多
BACKGROUND Type 2 diabetic nephropathy(T2DN)is a severe complication of diabetes mellitus,and identifying biomarkers for its prognosis remains a critical challenge.Previous studies have suggested potential roles of mi...BACKGROUND Type 2 diabetic nephropathy(T2DN)is a severe complication of diabetes mellitus,and identifying biomarkers for its prognosis remains a critical challenge.Previous studies have suggested potential roles of microRNAs(e.g.,miR-495-3p),adiponectin(ADPN),and cardiometabolic index(CMI)in metabolic and renal pathologies.However,their combined predictive value for T2DN prognosis is not well understood.AIM To explore serum miR-495-3p,ADPN,and CMI levels in T2DN and their value in predicting prognosis.METHODS A total of 98 T2DN patients(study group)and 49 type 2 diabetic patients with normal renal function(control group)were enrolled from February 2020 to February 2022.Serum levels of miR-495-3p,ADPN,and CMI were measured in both groups.Patients were followed up for 6 months to assess prognosis.Dif-ferences between groups were analyzed,and multivariate logistic regression and receiver operating characteristic(ROC)curve analyses were performed to eva-luate the predictive value of these biomarkers.RESULTS The study group exhibited significantly lower miR-495-3p levels and higher ADPN and CMI levels compared to the control group(P<0.05).Poor prognosis patients had even lower miR-495-3p and higher ADPN and CMI levels than those with good prognosis(P<0.05).Multivariate analysis identified alanine amino-transferase,aspartate aminotransferase,urea nitrogen,serum creatinine,miR-495-3p,ADPN,and CMI as independent predictors of prognosis(P<0.05).ROC analysis revealed area under the curve values of 0.762(miR-495-3p),0.902(ADPN),0.757(CMI),0.899(alanine aminotransferase),0.852(aspartate ami-notransferase),0.916(urea nitrogen),and 0.910(serum creatinine)for predicting poor prognosis(P<0.05).CONCLUSION Low miR-495-3p and high ADPN and CMI levels are linked to T2DN and poor prognosis,highlighting their potential for risk prediction and clinical management.展开更多
AIM： To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 o...AIM： To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level. METHODS： Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA. RESULTS： Systemic adiponectin is reduced in fatfed rats but is elevated in mice after bile duct ligation （BDL）. Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BE）L-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice. CONCLUSION： Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar findings have been described in humans. Diminished hepatic expression of adiponectin receptors was only found in liver cirrhosis.展开更多
The authors investigated the possible association of -4522C/T variation of adiponectin gene with coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Genotyping of SNP --4522C/T in 304 patients with C...The authors investigated the possible association of -4522C/T variation of adiponectin gene with coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Genotyping of SNP --4522C/T in 304 patients with CHD, 389 patients with T2DM, and 405 age and sex-matched healthy control subjects was carried out by means of PCR-RFLP approach. No significant difference in the genotype or allele frequencies was found, either between patients with CHD and control subjects, or between patients with T2DM and control subjects. However, in the subgroup analysis, an association of the TAr genotype and T allele with type 2 diabetes combined with obesity （BMI ≥ 25 kg/m2） was found （P = 0.014 and P = 0.034, respectively）. Also the homeostasis model assessment of insulin resistance （HOMA-IR） in T2DM patients with T/T genotype was significantly higher than that in T2DM patients carrying C allele （P = 0.0069）. The authors＇ findings for the first time demonstrated that SNP --4522 in the adiponectin gene was associated with T2DM that combined with obesity and higher insulin resistance index in patients with T2DM. This indicated that the variation might associate with an increased susceptibility to type 2 diabetic obesity and insulin resistance. But -4522C/T polymorphism did not contribute to the susceptibility of CHD.展开更多
[ Objective] The aim of this study was to provide a basis for study on adiponectin as a candidate gene for fat deposition. [ Method] The promoter sequence of adiponectin was obtained by porcine BAC library screening a...[ Objective] The aim of this study was to provide a basis for study on adiponectin as a candidate gene for fat deposition. [ Method] The promoter sequence of adiponectin was obtained by porcine BAC library screening and primer-walking method. The polymorphisms of adiponectin promoter from 290 pigs, including 5 breeds of Lantang pig, Large spotted pig, Large white pig, Landrace and Duroc, were analyzed with PCR-RFLP. [ Result] At SNP site of adiponectin 5＇-flanking region -1 010 bp （G/A）, GG genotype frequency in Chinese indigenous pigs was significantly higher than that in exotic pigs. At SNP site of adiponectin 5＇-flanking region -394 bp （T/C）, the genotype distribution of Chi- nese indigenous pigs was abundant, while no CC genotype was detected in exotic pigs, and T allele frequency was higher in exotic pigs. [ Conclusion] SNP site mutation of - 1 010 bp （G/A） may lead to changes of the gene transcription level, while SNP site of -394 bp （T/C） properly has no relationship with gene transcription level and fat deposition.展开更多
Adiponectin is an adipokine, which is expressed in adipose tissue and is thought to play an important role in glucose metabolism. Hypoadiponectinemia can cause reduction of fatty acid oxidation, decreased glucose upta...Adiponectin is an adipokine, which is expressed in adipose tissue and is thought to play an important role in glucose metabolism. Hypoadiponectinemia can cause reduction of fatty acid oxidation, decreased glucose uptake in skeletal muscle cells, and increased gluconeogenesis in hepatic cells. The level of plasma glucose can be increased. On the other hand, the decrease of fatty acid oxidation increases the level of free fatty acid （FFA）, which increases the insulin resistance, and then decreases the glucose uptake, which ultimately causes increased plasma glucose and type 2 diabetes （T2D）. This review describes the process from hypoadiponectinemia to T2D and the genesis of hypoadiponectinemia at a molecular level.展开更多
Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic eff...Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic effects on depressive disorders, although knowledge of the underlying mechanisms remains limited. Suppressed hippocampal neurogenesis in adult brains has been regarded, at least partly, contributive to depression, whereas physical exercise that restores neuro- genesis accordingly exerts the anti-depressive action. Several recent publications have suggested the potential role of adiponectin, a protein hormone secreted by peripheral mature adipocytes, in mediating physical exercise-triggered enhancement of hippocampal neurogenesis and alleviation of depression. Here, we briefly review these novel findings and discuss the possibility of counter- acting depression by modulating adiponectin signaling in the hippocampus with interventions including physical exercise and administration of pharmacological agents.展开更多
Adiponectin is known to play primary roles in the regulation of systemic glucose homeostasis and lipid metabolism. Interestingly, emerging evidence indicates beneficial effects of adiponectin on liver fibrosis; howeve...Adiponectin is known to play primary roles in the regulation of systemic glucose homeostasis and lipid metabolism. Interestingly, emerging evidence indicates beneficial effects of adiponectin on liver fibrosis; however, the exact mechanisms of this action remain unclear. Herein, we aimed to summarize the recent findings regarding the role of adiponectin in liver fibrogenesis and update the current comprehensive knowledge regarding usefulness of adiponectin-based treatments in liver fibrosis. Adiponectin has been demonstrated to have an anti-fibrotic action in the liver by blocking the activation of hepatic stellate cellmediated adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptoralpha pathways, which in turn diminish the expression of pro-fibrotic genes. In addition, hyperadiponectinemia was noted in patients with various chronic liver diseases(CLDs)-related liver fibrosis. An increase in circulating adiponectin levels was also found to be associated with the development of liver fibrosis, indicating a role of adiponectin as a non-invasive biomarker for predicting the progression of liver fibrosis. It is therefore reasonable to speculate that adiponectin may be developed as a new therapeutic candidate for the treatment of liver fibrosis. Nonetheless, future observations are still necessary to fully elucidate the extent of the effects of adiponectin onliver fibrotic outcomes, in order to modify adiponectin as an anti-fibrotic therapy that would speed up fibrosis reversal in patients with CLD.展开更多
In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical role...In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical roles in the pathogenesis of diabetes and metabolic syndrome. Here, we analyzed the endocytosis of adiponectin and adiponectin receptor 1 （AdipoR1） and found that they are both internalized into transferrin-positive compartments that follow similar traffic routes. Blocking clathrin-mediated endocytosis by expressing Eps15 mutants or depleting K^＋ trapped AdipoR1 at the plasma membrane, and K^＋ depletion abolished adiponectin internalization, indicating that the endocytosis of AdipoR1 and adiponectin is clathrin-dependent. Depletion of K^＋ and overexpression of Eps15 mutants enhance adiponectin- stimulated AMP-activated protein kinase phosphorylation, suggesting that the endocytosis of AdipoR1 might down-regulate adiponectin signaling. In addition, AdipoR1 colocalizes with the small GTPase Rab5, and a dominant negative Rab5 abrogates AdipoR1 endocytosis. These data indicate that AdipoR1 is internalized through a clathrin- and Rab5- dependent pathway and that endocytosis may play a role in the regulation of adiponectin signaling.展开更多
In order to confirm whether the mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were correlated with the serum parameters of glucose and lipid metabolism and to clarify ...In order to confirm whether the mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were correlated with the serum parameters of glucose and lipid metabolism and to clarify the regulation of adiponectin receptor gene expression in diabetic states, serum adiponectin, mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were examined in type 2 diabetic rats. The model of type 2 diabetes was prepared by feeding high fat diet and injecting low dosage of streptozotocin (STZ). The diabetic rats were screened out by oral glucose tolerance test. One group of type 2 diabetic rats received rosiglitazone. The serum adiponectin concentration was detected by using ELISA and mRNA levels were examined by RT-PCR. The serum adiponectin levels and mRNA levels of adiponectin in adipose tissue of type 2 diabetic rats were significantly decreased as compared with the normal control rats (P<0.05, P<0.01 respectively). No siglificant changes were observed in the expression of adiponectin receptor 1 in the skeletal muscle of type 2 diabetic rats. The mRNA levels of adiponectin in adipose tissue were reversely correlated with serum insulin (r=-0.66, P<0.05), triglyceride (r=-0.58, P<0.05), cholesterol (r=-0.49, P<0.05), interleukin-6 (r=-0.49, P<0.05) and tumor necrosis factor (r=-0.43, P<0.05). The expression of adiponectin receptors was not altered in the skeletal muscle of Type 2 diabetic rats. The decreased serum adiponectin was caused by the decreased expression of adiponectin mRNA in adipose tissue rather than the adiponectin receptors in the skeletal muscle, which could be improved by rosiglitazone.展开更多
基金supported by the National Natural Science Foundation of China,No.82072529(to HWHT)Key Laboratory of Guangdong Higher Education Institutes,No.2021KSYS009(to HWHT)the China Postdoctoral Science Foundation,No.2022M720907(to HHG)。
文摘Alzheimer's disease is the primary cause of dementia and imposes a significant socioeconomic burden globally.Physical exercise,as an effective strategy for improving general health,has been largely reported for its effectiveness in slowing neurodegeneration and increasing brain functional plasticity,particularly in aging brains.However,the underlying mechanisms of exercise in cognitive aging remain largely unclear.Adiponectin,a cell-secreted protein hormone,has recently been found to regulate synaptic plasticity and mediate the antidepressant effects of physical exercise.Studies on the neuroprotective effects of adiponectin have revealed potential innovative treatments for Alzheimer's disease.Here,we reviewed the functions of adiponectin and its receptor in the brains of human and animal models of cognitive impairment.We summarized the role of adiponectin in Alzheimer's disease,focusing on its impact on energy metabolism,insulin resistance,and inflammation.We also discuss how exercise increases adiponectin secretion and its potential benefits for learning and memory.Finally,we highlight the latest research on chemical compounds that mimic exerciseenhanced secretion of adiponectin and its receptor in Alzheimer's disease.
基金supported by STI2030-Major Projects,No.2022ZD0207600(to LZ)the National Natural Science Foundation of China,Nos.32070955(to LZ),U22A20301(to KFS)+3 种基金the Natural Science Foundation of Guangdong Province,No.2021A1515012197(to HO)Guangzhou Core Medical Disciplines Project,No.2021-2023(to HO)Key Research and Development Plan of Ningxia Hui Automomous Region,No.2022BEG01004(to KFS)Science and Technology Program of Guangzhou,China,No.202007030012(to KFS and LZ)。
文摘Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.
基金supported by grants from the National Natural Science Foundation of China (82160837)2019 Guangxi First-Class Discipline Construction Project (2019XK139)+3 种基金Qihuang Project High-level Talents Cultivation Program of Guangxi University of Chinese Medicine (2021007)2019 Traditional Chinese Medicine Inheritance and Innovation Talent Training Platform Construction Project (2019-41)Innovation Program of Guangxi Graduate Education of Guangxi University of Chinese Medicine (XYJ22024)2022 Guangxi (Young) Qihuang Scholar Training Program (2021-10)
文摘Background:Activation of NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)inflammasomes induced by pyroptosis is crucial in metabolic dysfunction-associated steatohepatitis(MASH)progression.Adiponectin possesses an anti-inflammatory role in various liver diseases.This study aimed to evaluate the effects of adiponectin on MASH.Methods:Adiponectin-mediated anti-inflammatory mechanisms,effects on pyroptosis-related proteins,and activation of NLRP3 inflammasomes were investigated using methionine-choline-deficient(MCD)-induced MASH murine model and in vitro models.The degree of MASH inflammation in liver tissue of C57BL/6J mice was assessed using histopathology.Enzyme-linked immunosorbent assay was performed to measure levels of inflammatory factors[interleukin-18(IL-18),IL-1β,and tumor necrosis factor-α(TNF-α)]in mice serum and culture medium.Western blot and quantitative polymerase chain reaction were performed to analyze the expression of pyroptosis-related genes and proteins in liver tissues of mouse model and in vitro models.Macrophage recruitment in vitro was evaluated using co-culture of upper and lower chambers.Results:MASH developed in MCD diet mice[metabolic dysfunction-associated steatotic liver disease(MASLD)activity score=6]but not in methionine-choline-sufficient(MCS)diet mice(MASLD activity score=3).Compared to MCS-fed mice,MCD-fed mice showed increased serum levels of aspartate amino-transferase,IL-18,IL-1β,and TNF-αand higher MASLD activity score(P<0.001).Adiponectin inhibited these increases(P<0.05)and suppressed mRNA and protein levels of NLRP3,gasdermin-D(GSDMD),and GSDMD-N in liver tissues(P<0.05).In vitro,lipopolysaccharide(LPS)/palmitic acid(PA)increased the levels of IL-18,IL-1β,and TNF-α,mRNA expressions of CASP1 and GSDMD,and production of CASP1,NLRP3,GSDMD,and GSDMD-N(P<0.01).Adiponectin reduced the levels of these inflammatory fac-tors and downregulated the mRNA expression and protein generation of pyroptosis-related markers(P<0.05).HepG2 cells pretreated with LPS/PA recruited more J774A.1 cells(P<0.001)and increased inflam-matory factor secretion by J774A.1 cells(P<0.001).Adiponectin inhibited this recruitment and reduced inflammatory factor secretion(P<0.001).Conclusions:Adiponectin inhibits hepatocyte pyroptosis by reducing the production and activation of NLRP3 inflammasomes,CASP1,and GSDMD,thus improving the inflammatory response in MASH and possibly delaying or reversing MASLD progression.
文摘BACKGROUND The persistent burden of cardiovascular(CV)disease in the United States requires innovative and cost-effective prognostic markers that can be relied upon.AIM To provide insights into how adiponectin can predict all-cause mortality and major adverse CV events(MACE)in patients with coronary artery disease(CAD)and to determine the prognostic value of adiponectin in predicting all-cause mortality and MACE in patients with stable CAD.METHODS We conducted a systematic search on PubMed,Scopus,and Google Scholar to find relevant studies published through June 2023 evaluating the long-term prognostic role of adiponectin in patients with stable CAD.Using a random effects model with 95%CI,we estimated the odds ratio(OR)while assessing heterogeneity through I^(2)statistics.To ensure robustness,we performed a sensitivity analysis using the leave-one-out approach.RESULTS After screening,we included five prospective studies involving 3225 patients who were followed up for a median duration of 3.8 years.Within the study population,prevalent risk factors included hypertension,diabetes,hyperlipidemia,and smoking.The commonly prescribed medications were angiotensin-converting enzyme inhibitors,beta blockers,and statins.The combined adjusted OR for all-cause mortality was found to be 2.51(95%CI:1.36–4.62),showing heterogeneity(I^(2)=65.51%,P=0.03).On the other hand,the combined adjusted OR for MACE was determined to be 1.04(95%CI:1.02–1.06)with no significant heterogeneity observed(I^(2)=0%,P=0.68).Through a sensitivity analysis,it was discovered that none of the studies significantly impacted the overall results of the meta-analysis,thus indicating their robustness.CONCLUSION Higher levels of adiponectin were found to be associated with an increased risk of long-term mortality and MACE in patients with CAD,which highlights its potential as a cost-effective marker for risk assessment and guiding treatment strategies.Further research on the role of adiponectin could greatly influence decision-making and resource allocation in CV care.
文摘BACKGROUND Type 2 diabetic nephropathy(T2DN)is a severe complication of diabetes mellitus,and identifying biomarkers for its prognosis remains a critical challenge.Previous studies have suggested potential roles of microRNAs(e.g.,miR-495-3p),adiponectin(ADPN),and cardiometabolic index(CMI)in metabolic and renal pathologies.However,their combined predictive value for T2DN prognosis is not well understood.AIM To explore serum miR-495-3p,ADPN,and CMI levels in T2DN and their value in predicting prognosis.METHODS A total of 98 T2DN patients(study group)and 49 type 2 diabetic patients with normal renal function(control group)were enrolled from February 2020 to February 2022.Serum levels of miR-495-3p,ADPN,and CMI were measured in both groups.Patients were followed up for 6 months to assess prognosis.Dif-ferences between groups were analyzed,and multivariate logistic regression and receiver operating characteristic(ROC)curve analyses were performed to eva-luate the predictive value of these biomarkers.RESULTS The study group exhibited significantly lower miR-495-3p levels and higher ADPN and CMI levels compared to the control group(P<0.05).Poor prognosis patients had even lower miR-495-3p and higher ADPN and CMI levels than those with good prognosis(P<0.05).Multivariate analysis identified alanine amino-transferase,aspartate aminotransferase,urea nitrogen,serum creatinine,miR-495-3p,ADPN,and CMI as independent predictors of prognosis(P<0.05).ROC analysis revealed area under the curve values of 0.762(miR-495-3p),0.902(ADPN),0.757(CMI),0.899(alanine aminotransferase),0.852(aspartate ami-notransferase),0.916(urea nitrogen),and 0.910(serum creatinine)for predicting poor prognosis(P<0.05).CONCLUSION Low miR-495-3p and high ADPN and CMI levels are linked to T2DN and poor prognosis,highlighting their potential for risk prediction and clinical management.
基金Supported by a grant from the Deutsche Forschungsgemeinschaft (BU 1141/3-2)
文摘AIM： To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level. METHODS： Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA. RESULTS： Systemic adiponectin is reduced in fatfed rats but is elevated in mice after bile duct ligation （BDL）. Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BE）L-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice. CONCLUSION： Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar findings have been described in humans. Diminished hepatic expression of adiponectin receptors was only found in liver cirrhosis.
基金the Chinese High Tech Programs (863) from the Ministry of Science and Technology (No. 2002BA- 711A08)the National Natural Science Foundation of China (No. 30671155, and 39993420)+1 种基金Grant FMU-RT002 of Program for Innovative Research Team in Science and Technology in Fujian Province Universitythe Science Foundation from the Depart-ment of Education of Fujian Province (No. JA05251, and JB06215).
文摘The authors investigated the possible association of -4522C/T variation of adiponectin gene with coronary heart disease （CHD） and type 2 diabetes mellitus （T2DM）. Genotyping of SNP --4522C/T in 304 patients with CHD, 389 patients with T2DM, and 405 age and sex-matched healthy control subjects was carried out by means of PCR-RFLP approach. No significant difference in the genotype or allele frequencies was found, either between patients with CHD and control subjects, or between patients with T2DM and control subjects. However, in the subgroup analysis, an association of the TAr genotype and T allele with type 2 diabetes combined with obesity （BMI ≥ 25 kg/m2） was found （P = 0.014 and P = 0.034, respectively）. Also the homeostasis model assessment of insulin resistance （HOMA-IR） in T2DM patients with T/T genotype was significantly higher than that in T2DM patients carrying C allele （P = 0.0069）. The authors＇ findings for the first time demonstrated that SNP --4522 in the adiponectin gene was associated with T2DM that combined with obesity and higher insulin resistance index in patients with T2DM. This indicated that the variation might associate with an increased susceptibility to type 2 diabetic obesity and insulin resistance. But -4522C/T polymorphism did not contribute to the susceptibility of CHD.
基金Supported by 948 Project from Ministry of Agriculture(2006-G50)~~
文摘[ Objective] The aim of this study was to provide a basis for study on adiponectin as a candidate gene for fat deposition. [ Method] The promoter sequence of adiponectin was obtained by porcine BAC library screening and primer-walking method. The polymorphisms of adiponectin promoter from 290 pigs, including 5 breeds of Lantang pig, Large spotted pig, Large white pig, Landrace and Duroc, were analyzed with PCR-RFLP. [ Result] At SNP site of adiponectin 5＇-flanking region -1 010 bp （G/A）, GG genotype frequency in Chinese indigenous pigs was significantly higher than that in exotic pigs. At SNP site of adiponectin 5＇-flanking region -394 bp （T/C）, the genotype distribution of Chi- nese indigenous pigs was abundant, while no CC genotype was detected in exotic pigs, and T allele frequency was higher in exotic pigs. [ Conclusion] SNP site mutation of - 1 010 bp （G/A） may lead to changes of the gene transcription level, while SNP site of -394 bp （T/C） properly has no relationship with gene transcription level and fat deposition.
文摘Adiponectin is an adipokine, which is expressed in adipose tissue and is thought to play an important role in glucose metabolism. Hypoadiponectinemia can cause reduction of fatty acid oxidation, decreased glucose uptake in skeletal muscle cells, and increased gluconeogenesis in hepatic cells. The level of plasma glucose can be increased. On the other hand, the decrease of fatty acid oxidation increases the level of free fatty acid （FFA）, which increases the insulin resistance, and then decreases the glucose uptake, which ultimately causes increased plasma glucose and type 2 diabetes （T2D）. This review describes the process from hypoadiponectinemia to T2D and the genesis of hypoadiponectinemia at a molecular level.
基金supported by Hong Kong Health and Medical Research FundLeading Talents of Guangdong(2013)+3 种基金Programme of Introducing Talents of Discipline to Universities(B14036)Project of International,as well as Hong Kong,Macao&Taiwan Science and Technology Cooperation Innovation Platform in Universities in Guangdong Province,China(2013gjhz0002)grants to Jinan University Guangdong-Hong Kong-Macao Cooperation and Innovation Center for Tissue Regeneration and RepairState Key Laboratory of Pharmaceutical Biotechnology,Hong Kong SAR,China
文摘Psychological depression is drawing accumulating attention nowadays, due to the skyrocketing incidence worldwide and the enormous burdens it incurs. Physical exercise has been long recog- nized for its therapeutic effects on depressive disorders, although knowledge of the underlying mechanisms remains limited. Suppressed hippocampal neurogenesis in adult brains has been regarded, at least partly, contributive to depression, whereas physical exercise that restores neuro- genesis accordingly exerts the anti-depressive action. Several recent publications have suggested the potential role of adiponectin, a protein hormone secreted by peripheral mature adipocytes, in mediating physical exercise-triggered enhancement of hippocampal neurogenesis and alleviation of depression. Here, we briefly review these novel findings and discuss the possibility of counter- acting depression by modulating adiponectin signaling in the hippocampus with interventions including physical exercise and administration of pharmacological agents.
基金Supported by The Research Chair Grant from NSTDA,No.P-15-50004the Center of Excellence in Clinical Virology,No.GCE 59-00930-005Department of Pediatrics,Faculty of Medicine,Chulalongkorn University and Hospital
文摘Adiponectin is known to play primary roles in the regulation of systemic glucose homeostasis and lipid metabolism. Interestingly, emerging evidence indicates beneficial effects of adiponectin on liver fibrosis; however, the exact mechanisms of this action remain unclear. Herein, we aimed to summarize the recent findings regarding the role of adiponectin in liver fibrogenesis and update the current comprehensive knowledge regarding usefulness of adiponectin-based treatments in liver fibrosis. Adiponectin has been demonstrated to have an anti-fibrotic action in the liver by blocking the activation of hepatic stellate cellmediated adenosine monophosphate-activated protein kinase and peroxisome proliferator-activated receptoralpha pathways, which in turn diminish the expression of pro-fibrotic genes. In addition, hyperadiponectinemia was noted in patients with various chronic liver diseases(CLDs)-related liver fibrosis. An increase in circulating adiponectin levels was also found to be associated with the development of liver fibrosis, indicating a role of adiponectin as a non-invasive biomarker for predicting the progression of liver fibrosis. It is therefore reasonable to speculate that adiponectin may be developed as a new therapeutic candidate for the treatment of liver fibrosis. Nonetheless, future observations are still necessary to fully elucidate the extent of the effects of adiponectin onliver fibrotic outcomes, in order to modify adiponectin as an anti-fibrotic therapy that would speed up fibrosis reversal in patients with CLD.
文摘In eukaryotic cells, receptor endocytosis is a key event regulating signaling transduction. Adiponectin receptors belong to a new receptor family that is distinct from G-protein-coupled receptors and has critical roles in the pathogenesis of diabetes and metabolic syndrome. Here, we analyzed the endocytosis of adiponectin and adiponectin receptor 1 （AdipoR1） and found that they are both internalized into transferrin-positive compartments that follow similar traffic routes. Blocking clathrin-mediated endocytosis by expressing Eps15 mutants or depleting K^＋ trapped AdipoR1 at the plasma membrane, and K^＋ depletion abolished adiponectin internalization, indicating that the endocytosis of AdipoR1 and adiponectin is clathrin-dependent. Depletion of K^＋ and overexpression of Eps15 mutants enhance adiponectin- stimulated AMP-activated protein kinase phosphorylation, suggesting that the endocytosis of AdipoR1 might down-regulate adiponectin signaling. In addition, AdipoR1 colocalizes with the small GTPase Rab5, and a dominant negative Rab5 abrogates AdipoR1 endocytosis. These data indicate that AdipoR1 is internalized through a clathrin- and Rab5- dependent pathway and that endocytosis may play a role in the regulation of adiponectin signaling.
文摘In order to confirm whether the mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were correlated with the serum parameters of glucose and lipid metabolism and to clarify the regulation of adiponectin receptor gene expression in diabetic states, serum adiponectin, mRNA levels of adiponectin in adipose tissue and mRNA levels of AdipoR1 in the skeletal muscles were examined in type 2 diabetic rats. The model of type 2 diabetes was prepared by feeding high fat diet and injecting low dosage of streptozotocin (STZ). The diabetic rats were screened out by oral glucose tolerance test. One group of type 2 diabetic rats received rosiglitazone. The serum adiponectin concentration was detected by using ELISA and mRNA levels were examined by RT-PCR. The serum adiponectin levels and mRNA levels of adiponectin in adipose tissue of type 2 diabetic rats were significantly decreased as compared with the normal control rats (P<0.05, P<0.01 respectively). No siglificant changes were observed in the expression of adiponectin receptor 1 in the skeletal muscle of type 2 diabetic rats. The mRNA levels of adiponectin in adipose tissue were reversely correlated with serum insulin (r=-0.66, P<0.05), triglyceride (r=-0.58, P<0.05), cholesterol (r=-0.49, P<0.05), interleukin-6 (r=-0.49, P<0.05) and tumor necrosis factor (r=-0.43, P<0.05). The expression of adiponectin receptors was not altered in the skeletal muscle of Type 2 diabetic rats. The decreased serum adiponectin was caused by the decreased expression of adiponectin mRNA in adipose tissue rather than the adiponectin receptors in the skeletal muscle, which could be improved by rosiglitazone.
